A commentary on “Models of Consent to Return of Incidental Findings in Genomic Research,” by Paul S. Appelbaum, Erik Parens, Cameron R. Waldman, Robert Klitzman, Abby Fyer, Josue Martinez, W. Nicholson Price II, and Wendy K. Chung, in the July‐August 2014 issue.

DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

Using artificial intelligence (AI) to make decisions in human resource management (HRM) raises questions of how fair employees perceive these decisions to be and whether they experience respectful treatment (i.e., interactional justice). In this experimental survey study with open-ended qualitative questions, we examine decision making in six HRM functions and manipulate the decision maker (AI or human) and decision valence (positive or negative) to determine their impact on individuals’ experiences of interactional justice, trust, dehumanization, and perceptions of decision-maker role appropriate- (...) ness. In terms of decision makers, the use of human decision makers over AIs generally resulted in better perceptions of respectful treatment. In terms of decision valence, people experiencing positive over negative decisions generally resulted in better perceptions of respectful treatment. In instances where these cases conflict, on some indicators people preferred positive AI decisions over negative human decisions. Qualitative responses show how people identify justice concerns with both AI and human decision making. We outline implications for theory, practice, and future research. (shrink)

Philosophers of well-being have tended to adopt a foundationalist approach to the question of theory and measurement, according to which theories are conceptually before measures. By contrast, social scientists have tended to adopt operationalist commitments, according to which they develop and refine well-being measures independently of any philosophical foundation. Unfortunately, neither approach helps us overcome the problem of coordinating between how we characterize well-being and how we measure it. Instead, we should adopt a coherentist approach to well-being science.

Generating an account that can sidestep the disagreement among substantive theories of well-being, while at the same time still providing useful guidance for well-being public policy, would be a significant achievement. Unfortunately, the various attempts to remain agnostic regarding what constitutes well-being fail to either be an account of well-being, provide useful guidance for well-being policy, or avoid relying on a substantive well-being theory. There are no theory-free lunches in well-being policy. Instead, I propose an intermediate account, according to which (...) well-being is constituted by endorsed veridical experiences. This account refers back to theories of well-being but does so as agnostically as possible. An intermediate account of well-being is meant as a policy guiding compromise between the different theories of well-being that make claims regarding what constitutes well-being. An intermediate account does as well as can be hoped for in providing a basis for well-being policy. (shrink)

It is an open question whether well-being ought to primarily be understood as a temporal concept or whether it only makes sense to talk about a person’s well-being over their whole lifetime. In this article, I argue that how this principled philosophical disagreement is settled does not have substantive practical implications for well-being science and well-being policy. Trying to measure lifetime well-being directly is extremely challenging as well as unhelpful for guiding well-being public policy, while temporal well-being is both an (...) adequate indirect measure of lifetime well-being, and an adequate focus for the purposes of improving well-being through public policy. Consequently, even if what we ought to care about is lifetime well-being, we should use temporal measures of well-being and focus on temporal well-being policies. (shrink)

Spoofing is the act of placing orders to buy or sell a financial contract without the intention to have those orders fulfilled in order to create the impression that there is a large demand for that contract at that price. In this article, I deny the view that spoofing in financial markets should be viewed as morally permissible analogously to the way bluffing is permissible in poker. I argue for the pro tanto moral impermissibility of spoofing and make the case (...) that spoofing is disanalogous from bluffing in at least one important regard—speculative trading serves an important economic role, whereas poker does not. (shrink)

van Els, Paul. "Echo's van de Weg" (Echoes of the Dao). Dutch translation of Huainanzi chapter 12. Het Trage Vuur 40 (December 2007): 29–35.

Policy-makers sometimes aim to improve well-being as a policy goal, but to do this they need some way to measure well-being. Instead of relying on potentially problematic theories of well-being to justify their choice of well-being measure, Daniel Hausman proposes that policy-makers can sometimes rely on preference-based measures as evidence for well-being. I claim that Hausman’s evidential account does not justify the use of any one measure more than it justifies the use of any other measure. This leaves us at (...) a loss as to which policy should be chosen in the non-trivial cases for which there is substantial disagreement between the different measures in their assessment of policy. (shrink)

Many philosophers reject the view that well-being over a lifetime is simply an aggregation of well-being at every moment of one's life, and thus they reject theories of well-being like hedonism and concurrentist desire satisfactionism. They raise concerns that such a view misses the importance of the relationships between moments in a person's life or the role narratives play in a person's well-being. In this article, we develop an atomist meta-theory of well-being, according to which the prudential value of a (...) life depends solely on the prudential value of each moment of that life. This is a general account of momentary well-being that can capture different features of well-being that standard atomistic accounts fail to capture, thus allowing for the possibility of an atomism that is compatible with a variety of well-being theories. Contrary to many criticisms leveled against momentary well-being, this well-being atomism captures all of the important features of well-being. (shrink)

in recent years, policy makers have shown increasing interest in implementing policies aimed at promoting individual well-being. But how should policy makers choose their well-being policies? a seemingly reasonable first step is to settle on an agreed-upon definition of well-being. yet there currently is significant disagreement on how well-being ought to be characterized, and agreement on the correct view of well-being does not appear to be forthcoming. Nevertheless, i argue in this paper that there are several reasons to think that (...) the domain of well-being in the public policy context is narrower than that of well-being in general, which makes agreement on how to understand well-being in the public policy context more likely. (shrink)

According to what I call the ‘argument from public bads’, if a researcher deceived subjects in the past, there is a chance that subjects will discount the information that a subsequent researcher provides, thus compromising the validity of the subsequent researcher’s experiment. While this argument is taken to justify an existing informal ban on explicit deception in experimental economics, it can also apply to implicit deception, yet implicit deception is not banned and is sometimes used in experimental economics. Thus, experimental (...) economists are being inconsistent when they appeal to the argument from public bads to justify banning explicit deception but not implicit deception. (shrink)

Linguistics of Saying is to be analyzed in the speech act conceived as an act of knowing. The speaking, saying and knowing subject, based on contexts and the principles of congruency and trust in the speech of other speakers, will create meanings and interpret the sense of utterances supplying the deficiencies of language by means of the intellective operations mentally executed in the act of speech. In the intellective operations you can see three steps or processes: first the starting point, (...) intuition or aísthesis; second, the process of abstraction; and third, the inverse: the process of determination or fixing the construct created. (shrink)

In book II of Plato’s Republic, Socrates discusses the cities of necessity and luxury (372d-373a). Discussions of these cities have often focused on citizens desiring more than they need, which creates a demand for luxury. Yet the second part of the equation, which is not usually recognized, is that there must be sufficient supply to meet this demand. The focus of this article is on the importance of supply in the discussion of the first two cities in book II of (...) the Republic. This article argues that the way Plato models the cities makes it the case that a surplus above levels of necessity will be generated from time to time. That the unwanted surplus cannot be spontaneously disposed of entails that the first two cities are institutionally incomplete. A government is needed in order to coordinate the disposal of the surplus supply the city will produce. (shrink)

Linguistics of saying studies language in its birth. Language is the mental activity executed by speaking subjects. Linguistics of saying consists in analyzing speech acts as the result of an act of knowing. Speaking subjects speak because they have something to say. Tthey say because they define themselves before the circumstance they are in. And this is possible because they are able to know. Speaking, then, is speaking, saying and knowing. In this sense there is a progressive determination. Knowing makes (...) possible saying, and saying determines speaking, or, in other words: speaking involves saying and knowing, and saying involves knowing. The problem thus is to determine the meaningful intentional purpose of the individual speaker to say something in every speech act. (shrink)

Philosophical discussions on cognition (ranging from computational and representational approaches to the 4E fra-mework), on the one hand, and those on sound and auditory per-ception, on the other, have hitherto remained apart. In this paper, the author addresses the concept of “auditory cognition”. While committing to the conceptual analysis of the latter, the author in-troduces the discussion of modality-specif ic approaches. Since the contributions made so far in the domain of the philosophy of sound and auditory perception are prone to (...) favor computational-repre-sentational approaches —e.g., the perceptual coherence model (Méndez-Martínez, 2022)—, the exploration of 4E possibilities will lay down a series of questions aimed to encourage future developers from that viewpoint. In that sense, the author explores conceptual entailments and connections between the genealogy of theories within the philosophy of sound and auditory perception, and the hypothesis of the extended cognition (EX). (shrink)

Why do we have social norms—of fairness, cooperation, trust, property, or gender? Modern-day Humeans, as I call them, believe these norms are best accounted for in cultural evolutionary terms, as adaptive solutions to recurrent problems of social interaction. In this paper, I discuss a challenge to this “Humean Program.” Social norms involve widespread behaviors, but also distinctive psychological attitudes and dispositions. According to the challenge, Humean accounts of norms leave their psychological side unexplained. They explain, say, why we share equally, (...) but not why we disapprove of those who don’t. I defend the Humean Program against this challenge. In particular, I suggest an idea for how to extend the Program to account for the psychological side of norms. Socially adaptive behaviors aren’t just likely to emerge in a group; They are also likely to be widely taught within it. The transmission of these behaviors through instruction explains why they are associated with distinctive normative attitudes and dispositions. These attitudes play a pedagogical role in helping transmit these behaviors to children and newcomers. (shrink)

In this paper we discuss James Buchanan’s contribution in the narrow domain of understanding committee voting under majority rule. We then go on to discuss Charles Plott’s seminal experimental work on the topic that sparked a wave of public choice experimental work. However, given Plott’s claims that Buchanan influenced him significantly, it is puzzling that his work with Morris Fiorina explores a question outside of those which Buchanan and Tullock found interesting. We suggest several ways to resolve this tension. Our (...) chapter concludes by discussing a lacuna in the experimental public choice literature in which Buchanan was particularly interested—logrolling, or vote trading. (shrink)

Alasdair MacIntyre argues that moral virtues are antithetical to what is required of those who trade in financial markets to succeed. MacIntyre focuses on four virtues and argues that successful traders possess none of them: (i) self-knowledge, (ii) courage, (iii) taking a long-term perspective, and (iv) tying one’s own good with some set of common goods. By contrast, I argue that (i)–(iii) are, in fact, traits of successful traders, regardless of their normative assessment. The last trait – caring about the (...) common good – is often counterproductive in most for-profit ventures, including trading, and so singling out traders is inappropriate. (shrink)

The move from open outcry to electronic trading added another responsibility to futures exchanges—that of matching orders between buyers and sellers. Matching systems can affect the level and speed of price discovery, the distribution of revenue, as well as the level of price efficiency of a given market. Whether the matching system is procedurally fair is another important consideration. I argue that while FIFO (First In First Out) is a fair procedure in principle and is perceived as the default matching (...) system, it is not a fair procedure in practice. Likewise, while pro rata is a fair procedure in principle, it is not so in practice. Nevertheless, both FIFO and pro rata are relics of an open outcry system. Instead, I propose an alternative approach to matching systems that builds on the strengths of electronic trading—the ability to randomize in real time. I introduce random selection for service (RSS) as a matching system that is procedurally fair both in principle and in practice. (shrink)

Categorization behavior can be fruitfully analyzed in terms of the trade‐off between as high as possible faithfulness in the transmission of information about samples of the classes to be categorized, and as low as possible transmission costs for that same information. The kinds of categorization behaviors we associate with conceptual atoms, prototypes, and exemplars emerge naturally as a result of this trade‐off, in the presence of certain natural constraints on the probabilistic distribution of samples, and the ways in which we (...) measure faithfulness. Beyond the general structure of categorization in these circumstances, the same information‐centered perspective can shed light on other, more concrete properties of human categorization performance, such as the results of certain prominent experiments on supervised categorization. (shrink)

Both Franz Brentano and Edmund Husserl addressed sound while trying to explain the inner consciousness of time and gave to it the status of a supporting example. Although their inquiries were not aimed at clarifying in detail the nature of the auditory experience or sounds themselves, they made some interesting observations that can contribute to the current philosophical discussion on sounds. On the other hand, in analytic philosophy, while inquiring the nature of sounds, their location, auditory experience or the audible (...) qualities and so on, the representatives of that trend of thought have remained silent about the depiction of sound and the auditory phenomena in the phenomenological tradition. The paper’s intention is to relate both endeavours, yet the perspective carried out is that of analytic philosophy and, thus, I pay special attention to conceptual analysis as a methodological framework. In this sense, I first explain what sound ontology is in the context of analytic philosophy and the views that it encompasses— namely, the Property View (PV), the Wave View (WV) and the Event View (EV)—. Secondly, I address the problems it entails, emphasising that of sound individuation. In a third section, I propose the possibly controversial conjunction of a “Brentano-Husserl Analysis of the Consciousness of Time” (for short “Brentano-Husserl analysis”) and outline the commonalities of both authors, without ignoring its discrepancies. My main focus is Husserl’s 1905 Vorlesungen zur Phänomenologie des Inneren Zeitbewusstseins. While addressing the Brentano-Husserl analysis, I elaborate on the problem of temporal and spatial extension (Raumlichkeit and Zeitlichkeit, respectively) of both consciousness and sound. Such comparison is a key one, since after these two developments, one can notice some theoretical movements concerning the shift of attention from sounds to the unity of consciousness, and how they mirror each other. After examining the controversial claims concerning the temporal and spatial extension of both consciousness and sound, I argue in the concluding paragraphs that while considering the accounts of sound ontology, the Brentano-Husserl analysis would probably endorse a Property View and that this could have interesting consequences for the issue of Sound Individuation. (shrink)

Language is nothing but human subjects in as much as they speak, say and know. Language is something coming from the inside of the speaking subject manifest in the intentional meaningful purpose of the individual speaker. A language, on the contrary, is something coming from the outside, from the speech community, something offered to the speaking subject from the tradition in the technique of speaking. The speech act is the performance of an intuition by the subject, both individual and social.

Some advances in bioethics regarding ethical considerations that arise in the context of medical research can also be relevant when thinking about the ethical considerations that arise in the context of SoTL research. In this article, I aim to bring awareness to two potential ethical challenges SoTL researchers might face when playing a dual role of teacher and researcher that are similar to the challenges physicians face in their dual role of physician and researcher. In this article, I argue that (...) two commonly discussed concerns in bioethics---the need for clinical equipoise and the possibility of a therapeutic misconception---have analogies when conducting some types of research on students. I call these counterparts educational equipoise and the educational misconception. (shrink)

This paper addresses the relationship between logic and phenomenology at a historical moment that precedes the big divide between analytic philosophy and phenomenology. In analysing alternative derivations of phenomenological logic, the discussion focuses on the case of two notorious neo-Kantian Mexican philosophers from the first half of the XXth century: Adalberto García de Mendoza and Francisco Larroyo. It is argued that both García de Mendoza and Larroyo made an original contribution to the discussion on the relationship between phenomenology and logic. (...) Further, this paper attempts to present a charitable portrait of both García de Mendoza and Larroyo in contrast to underrating approaches to both Mexican philosophers. In so doing, this paper adopts a historical—though not strictly biographical— perspective. While it is true that neither García de Mendoza nor Larroyo could be considered “phenomenologists” or “Husserl scholars” according to contemporary standards it is worth noticing that they engage in the discussion of phenomenological logic. Both authors had the project of developing a grounding logic for science and, as the article argues, both attempts could be even linked. Their project, however, was unfinished. The plan of this paper is as follows. The first section addresses the problem of the relationship between logic and phenomenology. The second one focuses on García de Mendoza’s contributions. The third one elaborates on Larroyo’s Logic of Sciences. And, finally, the fourth section elaborates on these Mexican philosophers’ contributions to education, making as well further observations concerning the similarities and differences between both authors. (shrink)

We aim to map out the points of confluence between phronesis and emotion, as well as the nature of this confluence. We do so based on philosophical and psychological explanations of emotions and phronesis. Making sound decisions, which requires phronesis, is an important matter, but its relationship with emotions has only just begun to be studied. We propose that the interplay between phronesis and emotion is possible (rather than inevitable) because both have a cognitive-behavioural structure and because emotions are hierarchical. (...) In the case of emotion, there are no gaps between the cognitive and behavioural dimensions, while phronetic acts can only manifest if cognitive and behavioural aspects are activated simultaneously. The confluence we identify is bidirectional and involves mutual enrichment in this dual dimension. On the one hand, phronesis enriches emotion because it involves extra subjective knowledge and allows emotion to be directed towards higher goals. On the other hand, emotions enrich phronesis because phronesis makes decisions based on sensitive preferences and because emotions confirm correctness in the context of moral decision making. Methodologically, this study is theoretical and interdisciplinary, as our approach is both philosophical and psychological. Philosophy helps us to improve the conceptual foundation of the construct, while psychology provides an analysis of the emotional process, allowing philosophy to understand how emotional evaluation-assessment and motivation lead to decision making. (shrink)

van Els, Paul. "Vier muren en een dak vormen geen huis" (Four Walls and a Roof Do Not Form a House). Review of 25 eeuwen oosterse filosofie, edited by Jan Bor and Karel van der Leeuw. China Nu 28, no. 4 (2003): 34–35.

Entre las virtudes de la explicación de Gewirth, destaca su potencial para delimitar el objeto de los derechos humanos y contener la expansión incontrolada del discurso de los derechos. Al ceñirse al contexto de la acción y a los rasgos necesarios para la agencia intencional, dicha explicación proporciona un fundamento basado en la autonomía y libertad de los agentes intencionales prospectivos, tan solo limitadas por aquellas exigencias racionales derivadas de la igual consideración del status moral de todos los demás agentes (...) intencionales prospectivos quienes, en última instancia, se identifican con la humanidad en su conjunto mediante las ideas implícitas de reciprocidad y responsabilidad moral por los actos propios. En definitiva, el argumento de Gewirth desemboca en el PCG para proporcionar un fundamento racional de los derechos humanos limitado a la estructura normativa de la acción, la agencia intencional prospectiva potencial o actual de todos los seres humanos y los bienes necesarios para la acción intencional: la libertad y el bienestar. (shrink)

El autor del artículo edita y estudia una inscripción funeraria inédita de época helenística encontrada en Aptera (Creta) por la arqueóloga griega V. Ninioú-Kindelí. El texto de la inscripción dice así: A) Σώσανδρος | Βίτωνος. B) Ἀμφιμήδης | Σωσάνδρω.

This paper proposes some guidelines for the undeveloped discussion of auditory epistemology. Auditory epistemology is an approach concerned with the perceptual basis for knowledge and belief, specifically around audition. The article pursues two goals. Firstly, it claims that addressing auditory perception from the viewpoint of epistemology is more fruitful than the discussion on phenomenology which has thus far dominated the debates in the literature on sound. Secondly, it elaborates a concrete proposal pertaining to the cooperation of sense-modalities. In so doing, (...) a model for “Perceptual Coherence” is suggested. The first section of the paper critically reviews the problem of perception as it is usually understood in traditional epistemology. An ensuing section outlines the model of perceptual coherence. (shrink)

In the realm of the philosophy of sounds and auditory experience there is an ongoing discussion concerned with the nature of sounds. One of the contestant views within this ontology of sound is that of the Property View, which holds that sounds are properties of the sounding objects. A way of developing this view is through the idea of dispositionalism, namely, by sustaining the theory according to which sounds are dispositional properties (Pasnau 1999; Kulvicki 2008; Roberts 2017). That portrayal, however, (...) is not sufficient, as it has not inquired the metaphysical debates about dispositions beyond the conditional analysis. In this paper, I try to advance this view by including recent developments (for instance Bird 2007; Vetter 2015) in the field of dispositionalism and I analyse whether this new version can sort out known and new objections to Property View. (shrink)

The renewed interest in concepts and their role in psychological theorizing is partially motivated by Machery’s claim that concepts are so heterogeneous that they have no explanatory role. Against this, pluralism argues that there is multiplicity of different concepts for any given category, while hybridism argues that a concept is constituted by a rich common representation. This article aims to advance the understanding of the hybrid view of concepts. First, we examine the main arguments against hybrid concepts and conclude that, (...) even if not successful, they challenge hybridism to find a robust criterion for concept individuation and to show an explanatory advantage for hybrid concepts. Then we propose such a criterion of individuation, which we will call ‘functional stable coactivation’. Finally, we examine the prospects of hybridism to understand what is involved in recent approaches to categorization and meaning extraction. 1 The Heterogeneity of Conceptual Representations2 Two Challenges for Hybrid Concepts: Individuation and Explanation2.1 The coordination criterion2.2 Concepts as constituents of thoughts3 Individuating Hybrids: Functional Stable Coactivation4 The Explanatory Power of Hybrid Concepts4.1 Categorization4.2 Meaning extraction4.2.1 Linguistic comprehension and rich lexical entries4.2.2 Polysemy and hybrid concepts5 Conclusion. (shrink)

This paper addresses the problem of sound individuation (SI) and its connection to sound ontology (SO). It is argued that the problems of SI, such as aspatiality, extreme individuation, indexical perplexity and duration puzzles are due to SO’s uncertainties. Besides, I describe the views in SO, including the wave view (WV), the property view (PV), and the event view (EV), as Casey O’Callaghan defends it. According to O’Callaghan, EV offers clear standards to individuate sounds. However, this claim is countered by (...) the consideration that any view could also defend the standards in SO, and thus, EV does not solve any of the problems mentioned above. As a way of showing the difficulties inherited by sound’s inner ontology, the problem of its linguistic representation is also addressed. The problem of SI can be developed within the frame of the philosophy of language and, specifically, regarding the discussion about mass vs count-­sortal terms. Is the term sound a mass or a count­-sortal? It is shown that, for reasons pertaining SO, the decision regarding the case of sound as a mass or count-­sortal term remains open. SI is, thus, covered from the SO to the philosophy of language. (shrink)

This article aims to theoretically analyse so-called character friendship from the perspective of emotions. From this angle, our research enables us to distinguish different types of emotions, and we propose a conceptual model of the hierarchy of the emotions of character friendship and their influence on social behaviour. With this model in hand, the article discusses whether other-oriented emotions fully explain the emotional underpinnings of character friendship. We find other-oriented emotions to be ambiguous because they may or may not be (...) selfless. Thus we question whether these emotions can adequately explain the bonding content of character friendship. We conclude that there is a higher affective tier related to moral emotions and moral behaviour, which we have labelled the ‘bonding feeling’. This feeling is described with reference to its historical precedents (Rof Carballo’s ‘affective warp’), thus explaining its particularity. (shrink)

Dysmenorrhea, or menstrual pain, is regularly suffered by 45 to 95% of menstruating women. Despite its prevalence, and despite the philosophical importance of pain as a general phenomenon, dysmenorrhea has been all but completely overlooked in contemporary analytic philosophy of mind. This paper aims at rectifying this situation. We single out three properties of what is often considered the paradigmatic case of painful experience, what we call injury-centered pains, and argue that dysmenorrhea does not have any of them, and hence (...) that it does not neatly conform to the injury-centered model of pain. This calls into question the centrality of the injury-centered model, and suggests novel research avenues within theoretical debates on affectivity. (shrink)

La lengua española nació cuando los hablantes del latín de la península Ibérica cambiaron de modo de pensar. Desde el pensar absoluto latino, asimilaron el pensar substantivo de los griegos a través del pensar cristiano. Haciendo una síntesis de estos tres pensares absolutos, crearon el pensar individual, el pensar abstracto y el pensar real. De este modo crearon lo que se puede designar como una ontología lingüística, la manifestación directa del pensar español. Los modos de pensar tienen que ver con (...) los modos de concebir lo que nos rodea. Ambos a dos preceden y determinan el pensamiento y la manifestación de las actividades libres del hombre, tanto si este es considerado individualmente, como si es considerado socialmente dentro del conjunto de hablantes que participan y contribuyen dentro de una comunidad lingüística. (shrink)

El lenguaje o la actividad cognoscitiva del ser humano que se debate en su lucha contra la circunstancia en la que le ha tocado vivir es hablar, decir y conocer. El hombre habla porque tiene algo que decir, dice porque se define a sí mismo ante la circunstancia en la que vive en cada momento, y esto es posible porque conoce de forma creativa. En este sentido el decir determina el hablar, por arriba, y el conocer por abajo. El conocer (...) humano empieza en una sensación sensible, la aísthesis, la cual es transformada en un universal, extracto o concepto, logos, el cual es el fruto de una serie de operaciones intelectivas realizadas por el propio sujeto en u solo acto, el acto único de hablar, decir y conocer. (shrink)

While scientific inquiry crucially relies on the extraction of patterns from data, we still have a far from perfect understanding of the metaphysics of patterns—and, in particular, of what makes a pattern real. In this paper we derive a criterion of real-patternhood from the notion of conditional Kolmogorov complexity. The resulting account belongs to the philosophical tradition, initiated by Dennett :27–51, 1991), that links real-patternhood to data compressibility, but is simpler and formally more perspicuous than other proposals previously defended in (...) the literature. It also successfully enforces a non-redundancy principle, suggested by Ladyman and Ross, that aims to exclude from real-patternhood those patterns that can be ignored without loss of information about the target dataset, and which their own account fails to enforce. (shrink)

(This is one of the essays to be included in a book examining the causes of day-to-day strife in the populations of modern democracies vying to live and assert the freedoms promised to them by systems of governance supposed and expected to represent them.) -/- ... Such intelligence could be compared to a rocket that crosses up into the thermosphere dropping to destruction the thrust engine that got it there, downwards into the lower mesosphere, after leaving behind its satellite payload (...) in orbit. Or perhaps more appropriately, intelligence mirrors the movement of a plant pushing through soil upwards but also downwards into its roots (positive and negative phototropism and gravitropism), emerging without direct exposure to the sun yet ever dependent on its light, developing its embryonic stem and leaf systems to produce flowers and fruit, all the way changing and simultaneously shedding the forms of its evolving nature to achieve the fulfilment of all its functions in the creation and production of independent, fertile, self-regenerating seed past the impasse of change, loss, and even death. ... (shrink)

In the replies to my critics that follow I offer a more detailed account of the specific papers that they discuss or examine. The papers that they are especially concerned with are: “The Material World and Natural Religion in Hume’s Treatise” (Ryan) [Essay 3], “Hume’s Skepticism and the Problem of Atheism” (Fosl) [Essay 12], and “Hume’s Philosophy of Irreligion and the Myth of British Empiricism (Gautier) [Essay 16].

(This is one of the essays to be included in a book examining the causes of day-to-day strife in the populations of modern democracies vying to live and assert the freedoms promised to them by systems of governance supposed and expected to represent them.) -/- The emigrant / immigrant / migrant makes a conscious, relatively difficult decision to exchange what s/he knows for what is not known at all but in promise. The choice is often stark and carries with it (...) the imposition of restrictions on what will be possible in terms of existing customs, culture, and direct involvement with friends and family, and signifies a leap of faith into what appears to be a better, more prosperous, happier future. -/- At times, such choice is unavoidable, others it turns out to be a gamble of sorts, but, no matter what the cause, reason, or desire underlying an act of migration away from what the emigrant has known, it never turns out to be what was expected and no amount of preparation allows the emigrant to anticipate what will in fact occur. Migration is the founding of a new life in all the aspects of the emigrant’s existence. (shrink)

What was René Girard’s attitude towards philosophy? What philosophers influenced him? What stance did he take in the philosophical debates of his time? What are the philosophical questions raised by René Girard’s anthropology? In this interview, Paul Dumouchel sheds light on these issues.

Using the method of Descriptive Experience Sampling, some subjects report experiences of thinking that do not involve words or any other symbols [Hurlburt, R. T., and C. L. Heavey. 2006. Exploring Inner Experience. Amsterdam: John Benjamins; Hurlburt, R. T., and S. A. Akhter. 2008. “Unsymbolized Thinking.” Consciousness and Cognition 17 : 1364–1374]. Even though the possibility of this unsymbolized thinking has consequences for the debate on the phenomenological status of cognitive states, the phenomenon is still insufficiently examined. This paper analyzes (...) the main properties of unsymbolized thinking and advances an explanation of its origin. According to our analysis, unsymbolized thoughts appear as propositional states, that is, they are experienced as compositional conceptual phenomena, with semantic and syntactic features analogous to those of the contents of utterances. Based on this characterization, we hypothesize that UT is continuous with the activity of inner speech, in particular, it i... (shrink)

(This is one of the essays to be included in a book examining the causes of day-to-day strife in the populations of modern democracies vying to live and assert the freedoms promised to them by systems of governance supposed and expected to represent them.) "The artisan of old, the artist, the researcher, the developer, and the scientist today have this in common, that in refining, perfecting and pushing the boundaries of their respective crafts, they cannot achieve satisfaction or adequately perform (...) without simultaneously and progressively adapting, re-configuring, developing, and continuously changing the techniques and approaches they employ together with the tools and parameters for gauging actual success within the realm that only rigorous acquaintance, imaginative freedom, cross-functional, multifaceted learning, and distributive interaction may allow.". (shrink)

We explore the contribution made by oscillatory, synchronous neural activity to representation in the brain. We closely examine six prominent examples of brain function in which neural oscillations play a central role, and identify two levels of involvement that these oscillations take in the emergence of representations: enabling (when oscillations help to establish a communication channel between sender and receiver, or are causally involved in triggering a representation) and properly representational (when oscillations are a constitutive part of the representation). We (...) show that even an idealized informational sender–receiver account of representation makes the representational status of oscillations a non-trivial matter, which depends on rather minute empirical details. (shrink)

Imperativism is the view that the phenomenal character of the affective component of pains, orgasms, and pleasant or unpleasant sensory experience depends on their imperative intentional content. In this paper I canvass an imperativist treatment of pains as reason-conferring states.

Mi concepción sobre el lenguaje parte de tres realidades ciertas: el hablar (Coseriu), el decir (Ortega y Gasset), y el conocer (Descartes, Kant, Ortega y Gasset), tres realidades tan ciertas como que yo vivo porque estoy haciendo algo ahora mismo. Y este hacer algo constituye mi vida (Ortega y Gasset). Yo soy porque vivo y porque tengo la necesidad de hablar con otros seres humanos, quienes constituyen mi circunstancia, para definirme a mí mismo (decir) sobre aquello de lo que hablo (...) para conseguir un fin, aunque este sólo sea pasajero y volátil. La aparición del hablar, decir y conocer en el acto lingüístico nos revela el pensamiento y lo que llamamos el lenguaje y la lengua. Además, estas realidades radican en mí, en el ser humano, y manifiestan la condición de ser del ser humano, quien es capaz de conocer creativamente, definirse ante la situación que analiza antes de hablar (=decir), y de hablar utilizando palabras que no son suyas sino de la comunidad lingüística (=la lengua, Coseriu) en la que vive (Ortega y Gasset). Así, pues, considero el lenguaje como realidad que subyace en la conciencia del ser humano individual que habla, dice y conoce. (shrink)

Recasting Hume and Early Modern Philosophy is a collection of essays that are all concerned with major figures and topics in the early modern philosophy. Most of the essays are concerned, more specifically, with the philosophy of David Hume (1711-1776). The sixteen essays included in this collection are divided into five parts. These parts are arranged under the headings of: (1) Metaphysics and Epistemology; (2) Free Will and Moral Luck; (3) Ethics, Virtue and Optimism; (4) Skepticism, Religion and Atheism; and (...) (5) Irreligion and the Unity of Hume’s Thought. A particularly important theme running through many of these essays is the subject of Hume’s irreligious aims and intentions. The fifth and final part of the collection is devoted to an articulation and defence of this specific understanding of Hume’s philosophical thought. (shrink)